ARHGEF28

Rho guanine nucleotide exchange factor 28, the group of Dbl family Rho GEFs

Basic information

Region (hg38): 5:73626158-73941993

Links

ENSG00000214944 ∙ NCBI:64283 ∙ OMIM:612790 ∙ HGNC:30322 ∙ Uniprot:Q8N1W1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis (Moderate), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGEF28 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGEF28 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	13	24
missense			133	17	14	164
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1	1	4
non coding			1	2	77	80
Total	0	0	135	30	104

Variants in ARHGEF28

This is a list of pathogenic ClinVar variants found in the ARHGEF28 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-73684549-T-G			Benign (Jun 19, 2021)
5-73684867-A-C		not specified	Uncertain significance (Oct 08, 2024)
5-73684870-G-A		ARHGEF28-related disorder	Uncertain significance (Dec 05, 2022)
5-73685012-G-A			Benign (Jun 18, 2021)
5-73685044-G-C			Benign (Jun 18, 2021)
5-73749597-G-C			Benign (Jun 18, 2021)
5-73749654-A-G			Benign (Jun 19, 2021)
5-73749681-T-C			Benign (Jun 18, 2021)
5-73749839-G-A		ARHGEF28-related disorder	Likely benign (Jun 06, 2019)
5-73749843-A-G		not specified	Uncertain significance (Apr 24, 2024)
5-73749936-A-G		ARHGEF28-related disorder • not specified	Likely benign (Apr 07, 2023)
5-73749949-G-A		not specified	Uncertain significance (Aug 27, 2024)
5-73752926-A-T		not specified	Uncertain significance (Jan 12, 2024)
5-73752927-C-T		ARHGEF28-related disorder	Likely benign (Sep 20, 2017)
5-73752928-G-A		ARHGEF28-related disorder	Likely benign (Apr 20, 2022)
5-73752977-A-G		not specified	Uncertain significance (Aug 02, 2021)
5-73752992-G-C		not specified	Uncertain significance (Oct 29, 2021)
5-73752994-G-A		not specified	Benign (-)
5-73753001-G-A		ARHGEF28-related disorder	Uncertain significance (Aug 01, 2024)
5-73753041-C-T		not specified	Uncertain significance (Nov 22, 2024)
5-73753042-G-T		not specified	Benign/Likely benign (Dec 31, 2019)
5-73753050-A-G			Benign (May 01, 2023)
5-73753079-C-T		ARHGEF28-related disorder	Likely benign (Feb 15, 2023)
5-73753087-C-T		ARHGEF28-related disorder	Likely benign (May 31, 2023)
5-73753101-C-T		not specified	Uncertain significance (Jan 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGEF28	protein_coding	protein_coding	ENST00000545377	36	315836

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.10e-21	1.00	124544	1	118	124663	0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.734	823	884	0.931	0.0000485	11235
Missense in Polyphen		200	254.12	0.78702		3426
Synonymous	1.61	313	351	0.890	0.0000209	3275
Loss of Function	3.83	47	85.1	0.552	0.00000435	1083

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00102	0.00101
Ashkenazi Jewish	0.000202	0.000199
East Asian	0.000626	0.000612
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000357	0.000345
Middle Eastern	0.000626	0.000612
South Asian	0.00124	0.00118
Other	0.000340	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Functions also in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity). {ECO:0000250}.
• Pathway: Developmental Biology;EPH-Ephrin signaling;EPHB-mediated forward signaling;Axon guidance;Signaling events mediated by focal adhesion kinase;Regulation of RhoA activity (Consensus)

Intolerance Scores

• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.462
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Arhgef28
• Phenotype: normal phenotype; growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: arhgef28a
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: cell differentiation;regulation of Rho protein signal transduction;intracellular signal transduction;ephrin receptor signaling pathway
• Cellular component: cytosol;plasma membrane
• Molecular function: RNA binding;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;metal ion binding